This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wolfe, M. L. Articles by Rader, D. J. Search for Related Content PubMed PubMed Citation Articles by Wolfe, M. L. Articles by Rader, D. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Coronary Artery Disease Related Collections Cardiovascular Pharmacology Pathophysiology Risk Factors Chronic ischemic heart disease Genetics of cardiovascular disease Lipid and lipoprotein metabolism Related Article

(Circulation. 2004;110:1338-1340.)
© 2004 American Heart Association, Inc.

Editorial

Cholesteryl Ester Transfer Protein and Coronary Artery Disease

An Observation With Therapeutic Implications

Megan L. Wolfe, BS; Daniel J. Rader, MD

From the Center for Experimental Therapeutics and Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pa.

Correspondence to Daniel J. Rader, Center for Experimental Therapeutics and Department of Medicine, University of Pennsylvania School of Medicine, 654 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104. E-mail rader@mail.med.upenn.edu

Key Words: Editorials • cholesterol • lipoproteins • atherosclerosis • coronary disease

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Plasma levels of high-density lipoprotein cholesterol (HDL-C) are strongly inversely associated with risk of atherosclerotic cardiovascular disease (ASCVD). It has been estimated that for every 1-mg increase in HDL-C, there is a 2% to 3% decrease in cardiovascular risk,¹ which suggests that therapy to increase HDL-C levels could be effective in reducing cardiovascular risk. HDL metabolism is therefore a major emerging target for drug discovery.² The finding more than a decade ago that genetic deficiency of the cholesteryl ester transfer protein (CETP) in humans is associated with markedly elevated plasma HDL-C levels led to the concept that CETP inhibition could be a therapeutic strategy for raising HDL.³ Indeed, 2 small-molecule inhibitors of CETP have been shown to raise HDL-C levels in humans,^4–6 and this finding has generated substantial enthusiasm for CETP inhibition as a therapeutic strategy.

See p 1418

Important questions remain about whether CETP inhibition, despite its positive effects on HDL-C levels, will reduce ASCVD. One theoretical concern is that CETP inhibition could slow the rate of reverse cholesterol transport (RCT), the process by which macrophage cholesterol in the vessel wall is returned to the liver for excretion. In studies in humans, radiolabeled cholesteryl esters that originated in HDL ultimately appeared in the bile primarily after their transfer (presumably mediated by CETP) to apolipoprotein B-containing lipoproteins,⁷ which suggests that CETP might play an important physiological role in RCT. Ultimately, randomized controlled trials of CETP inhibitors will definitively address their effect on atherosclerosis and cardiovascular events. In the meantime, observational . . . [Full Text of this Article]

Related Article:

Plasma Levels of Cholesteryl Ester Transfer Protein and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The Prospective EPIC (European Prospective Investigation into Cancer and nutrition)–Norfolk Population Study

S. Matthijs Boekholdt, Jan-Albert Kuivenhoven, Nicholas J. Wareham, Ron J.G. Peters, J. Wouter Jukema, Robert Luben, Sheila A. Bingham, Nicholas E. Day, John J.P. Kastelein, and Kay-Tee Khaw
Circulation 2004 110: 1418-1423. [Abstract] [Full Text]

This article has been cited by other articles:

				M. Cuchel and D. J. Rader Is the Cholesteryl Ester Transfer Protein Proatherogenic or Antiatherogenic in Humans? J. Am. Coll. Cardiol., November 13, 2007; 50(20): 1956 - 1958. [Full Text] [PDF]

				A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF]

				D. Duffy and D. J. Rader Emerging Therapies Targeting High-Density Lipoprotein Metabolism and Reverse Cholesterol Transport Circulation, February 28, 2006; 113(8): 1140 - 1150. [Full Text] [PDF]